19-55948229-C-G

Variant names:

• chr19-55948229-C-G
• ENST00000291971.7:c.327C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000291971.7(NLRP8):​c.327C>G​(p.Asn109Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NLRP8 ENST00000291971.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.244
• Publications: 0 publications found

Genes affected

NLRP8 (HGNC:22940): (NLR family pyrin domain containing 8) This gene encodes a member of the nucleotide-binding oligomerization domain/ leucine rich repeat/ pyrin domain containing (NLRP) subfamily, which belongs to the Nod-like receptor family of proteins. NLRP genes play roles in the mammalian innate immune system through inflammasome formation and activation of caspases. In addition, NLRP genes have been found to function during mammalian reproduction. Consistent with a function during human preimplantation development, this gene is expressed at high levels in oocytes with decreased levels in embryos. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26902753).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000291971.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP8	NM_001433706.1		c.327C>G	p.Asn109Lys	missense	Exon 1 of 10	NP_001420635.1
	NLRP8	NM_001317000.1		c.327C>G	p.Asn109Lys	missense	Exon 1 of 10	NP_001303929.1	Q86W28-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP8	ENST00000291971.7	TSL:1 MANE Select	c.327C>G	p.Asn109Lys	missense	Exon 1 of 10	ENSP00000291971.3	Q86W28-1
	NLRP8	ENST00000590542.1	TSL:1	c.327C>G	p.Asn109Lys	missense	Exon 1 of 10	ENSP00000468121.1	Q86W28-2
	NLRP8	ENST00000850972.1		c.327C>G	p.Asn109Lys	missense	Exon 1 of 10	ENSP00000521054.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.24
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.15
Sift	Benign	0.078	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.21
MutPred		0.68		Gain of methylation at N109 (P = 0.0216)
MVP		0.27
MPC		0.39
ClinPred		0.34	T
GERP RS		-4.5
PromoterAI		-0.0075	Neutral
Varity_R		0.15
gMVP		0.16
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr19-56459595;